First of all I would like to express my appreciation
for the invitation to lecture here at this colloquium. I have attempted to
prepare my material in such a way as to make it relatively easy for all those
present to understand, keeping in mind that the audience is comprised of
representatives of various professions and different branches of medicine.

Preconditions for Organ Transplantation

What are the conditions required for organ
transplantation to be carried out?

Firstly, it must be surgically possible
to disconnect the whole organ, and to transfer it from the body of one person
to another in its entirety. Secondly, a critical factor (and the one that
causes the most problems, even today) is rejection of the transplanted organ by
the recipient. Thirdly, and no less important, is the location of a suitable
organ, from a live or deceased donor, in a state that will allow it to be
transplanted. I emphasize, "in a state that will allow it to be
transplanted," for this is a point of much ethical debate and discussion.
Organs obtained for transplant can be unsuitable for various reasons and can
often harm the patient receiving the transplant.

Historical
Background

The history of organ transplantation is lengthy. In the Middle Ages the
possibility of organ transplants had already been considered, and evidence for
it exists in the literature, particularly Christian texts which describe
attempts by various monks to exchange organs. A famous illustration from the
fifteenth century shows a patient undergoing “transplantation” of a leg in
which decomposition has spread. But real organ transplantation began only in
1902, when Karl, a French surgeon working in the United States, demonstrated a
technique for connecting blood vessels. This represented the first serious
basis for transplants.

In 1936 a first attempt was made by a Russian surgeon, Varonoy, to
transplant a kidney in a person who was about to die of kidney failure. The
transplant held for thirty-six hours, and then the patient died. The concept of
rejection was as yet unknown, as were other problems with which we are familiar
today. It is important to note the breakthrough by Sir Peter Midber, who was
the first to note the process of rejection (first and second set rejection),
introducing the study and understanding of organ rejection.

In 1951 a French surgeon, Kuss, was the first to describe the place in
the groin where the kidney is transplanted, and in 1954 David Hume (in Boston) performed the first transplant between identical twins, thus overcoming the
problem of rejection, and the kidneys actually functioned. In 1955 it was once
again Hume who transplanted kidneys from one person to another, carrying out
nine such transplants which lasted a number of months. At that time steroids
were already in use, but they caused numerous infections: the kidneys were
rejected, and most of the patients died. Hume admitted that kidney transplants
were still in their early stages, and supported the view that steroids are of
no benefit in these transplants.

In 1959 Hamburge, from the Keer Hospital in Paris, applied total body
radiation on patients in order to prevent rejection. Indeed, following his
transplantation of kidney, his patients functioned very well as long as he kept
them in total isolation. As soon as the patients were taken out of isolation,
they contracted infections.

The real move towards clinical transplants took place in 1962, when Tom
Sterszal began transplanting organs with the help of immunosuppressives, using
a method similar to that which we use today. In 1966 the HLA system was
discovered, assisting in the determination of organ compatibility, and in 1980 a new breakthrough was achieved: following studies by a Swiss researcher named Borel (from the
Sandoz company) a new immunosuppressive substance preventing rejection was
discovered - Cyclosporin A, which is still widely used.

Dangers
of Organ Transplants

What dangers are associated with organ transplants? Firstly, there can
be a technical failure with the connection of the actual organ. Whether it be
obstruction of the veins or arteries or whether it involve connection of a kidney
and ureter there are problems related to the surgical technique on one hand,
and problems related to rejection of the transplanted organ on the other.

It is important to note that the organs which are regularly
transplanted can be divided into two types. The first type consists of organs
which have no mechanical replacement, such as the liver or the heart. In the
event of the transplant failing, a repeat transplant is immediately required.
This poses a very serious problem as there is no “dialysis” for a liver or
heart. If someone undergoes a heart or liver transplant and the organ does not
function, a new transplant is immediately required. Hence for every transplant
of this type, planning is required as to where another heart or liver will be
obtained for a repeat transplant. Transplantation of the second type of organ,
for example kidneys, is easier, for if the new kidney is rejected, the
possibility exists of returning to dialysis.

An additional problem in organ transplantation is the issue of the serious
infections which attack patients receiving immunosuppressive treatment. The
most important issue today, and one which is constantly debated, is the
question of choosing organs which will be compatible and which will not be
damaged as a result of being removed from the donor's body. There are cases of
serious infection following transplants, a phenomenon which occurs principally
in patients receiving immunosuppressive therapy. The infection is likely to
attack specifically those patients who receive damaged organs when the
attending surgeons and doctors use strong immunosuppressive treatment to
suppress rejection and to combat the problem of the damaged organ.

Which organs are transplanted today? Clinical transplants of the
following have been carried out for many years: kidneys (since 1962), liver
(since 1963), heart and lungs (since 1968), and in recent years pancreas and
intestines. I have not mentioned skin transplants or corneas since these do not
require connection of blood vessels.

Kidney Transplants and Trade in Organs

I shall begin with kidney transplants,
which are routinely carried out almost worldwide. The kidney may come from a
living relative, a live donor who is not related, or from a dead donor.

Let us concentrate on the second category: a live donor who is not
related. We have here a person who, from the point of view of the result of the
transplant, is comparable to a dead donor since he is not related to the
recipient of the organ. Owing to the huge shortage of organs, an organ trade exists
in the world today and it is well known that kidneys may be bought from live
donors not related to the patient. In India, for example, there is a lively
trade in organs. People from all over the world travel to India in order to buy kidneys, and even undergo the transplants there. An organ trade also
exists in Egypt.

There are well-founded rumors from South America concerning the kidnapping of children, particularly from the poorer sectors,
supposedly with the purpose of taking them to resorts for treatment and
support. These children disappear, and it is believed that their organs are
removed and sold to people who are prepared to pay for them. With evidence of
such trade going on worldwide, we are particularly careful in Israel to avoid reaching a similar situation. But we do treat Israeli patients who have
undergone organ transplants in India, particularly kidney transplants, and who
come back to us for continued treatment following the operation.

A review of the results of kidney
transplants shows that there is 90% success during the first year for kidneys
from live relatives, and 75% success during the first year from dead donors.
Currently there are approximately one hundred transplants carried out each year
in Israel, with the demand reaching around two hundred and fifty. It must be
pointed out that the organ-demand curve in recent years has continually risen,
while the supply of organs has remained constant since the source for organs
remains more or less the same. The demand curve rises exponentially, and the
discrepancy between demand and supply is continually growing, giving rise to
various phenomena which are entirely unethical.

Following the transplant, an angiograph may be carried out in order to
show the artery of the leg on one side and the artery of the kidney on the
other. The artery of the kidney is attached to the artery of the leg, and the
angiograph shows the kidney very clearly, with the different branches of the
artery feeding it.

A kidney removed from the body too long after death may be damaged, and
will not function following transplantation.

Liver Transplants

Let us turn our attention to liver transplants. The first was carried
out in 1963 by Professor Tom Sterszal in Denver, Colorado. Thereafter he
continued to transplant livers, together with very few others (one surgeon in South Africa, and Prof. Kilna in Cambridge, for instance). A number of problems were encountered,
many of which have been solved with progress in surgical procedure. In a liver
transplant there are several blood vessels which have to be connected,
including the bile ducts. There are problems associated with the
size-compatibility of the organ, particularly when an adult's liver is
transplanted into a child.

In the event of definitive rejection of the organ which cannot be
suppressed by immunosuppressive treatment, a new organ must immediately be
transplanted, and any available source is approached for this purpose since
without a liver the patient will die.

Owing to the shortage of organs from
dead donors, attempts are being made to use live donors - a relative of the
patient, most often parents to children - and to remove just a portion of the
liver. In the case of dead donors, the liver is divided into two in order that
one organ can be used for two patients, even though this is much
more complicated and presents a certain level of danger to the recipients.

Liver transplants are still carried out
only in large medical centers, unlike kidney transplants which are much simpler
and are executed routinely in most hospitals, even the smaller ones.

Cyclosporin A and Heart Transplants

Now for a completely different topic, that of Cyclosporin A. Until
1980, transplants, especially of kidneys, were a subject taken mostly for
granted probably because the success rate for transplants involving heart,
liver, pancreas and other organs was not all that high. The turning point
occurred with the discovery of Cyclosporin A, a more potent immunosuppressive
substance, which was put into use during 1980-1. Since then transplant results
have improved dramatically, and even the curves for heart, liver, pancreas and
other organs have become exponential.

Heart transplants began in 1968. This first was carried out in South Africa by Christiaan Barnard, although there are those who insist that the road was already
paved for him by the laboratory work of Dr. Kantrowitz in California. In any
event, following that operation, many attempted heart transplants, but owing to
the continuing high rate of failure, enthusiasm waned considerably. Few centers
made further attempts at heart transplants. This was, as mentioned, until the
beginning of the 1980's, when Cyclosporin began to be used, and since then
heart transplants have become "routine" and are carried out in many
medical centers.

As mentioned, the problem with a heart
transplant is that if there is rejection, we attempt to control it using
immunosuppressives. But if this is unsuccessful, a repeat transplant needs to
be carried out immediately.

The life expectancy today for one year after a heart transplant is
about 50% - 60%.

Lung
Transplants

A lung transplant is required in the case of chronic lung failure. The
number of patients requiring such a procedure is constantly rising. The
transplant is complicated, since the lung is very sensitive owing to various
factors in the lung tissue, and hence the failure rate is high. There are only
a few medical centers in the world where lung transplants are carried out. At
first the practice was to transplant the heart and lung as one unit, but today
sufficient experience exists for the transplant of a lung alone to be
performed.

Pancreas
Transplants

Pancreas transplants, too, are becoming increasingly common. The
indication for a pancreas transplant is severe diabetes, especially juvenile
diabetes, which affects the kidneys. (Hence some patients undergo transplant of
kidney and pancreas.) The organ can come from a dead donor or from a live
relative. Experiments have been carried out at the University of Minnesota, where a good procedure has been developed for transplantation of a portion of the
pancreas from a living relative.

Some fairly serious technical problems
continue to complicate the connection of the transplanted portion of the
pancreas into the body of the recipient. The pancreas must also be connected
to the bladder, into which its secretions must flow.

During the 1980's a revolution occurred
in the area of pancreas transplants, as with other organs, and the number of
transplants started rising exponentially, as did the life expectancy figures
for the organs transplanted. This was due not only to the introduction of
Cyclosporin, but also to the increased skill of the surgeons. With a growing
number of such operations their experience in pancreas transplants increased,
and the results improved accordingly.

Intestine
Transplants

The transplant of intestines is also an important development. There
are many patients whose intestines cease to function as a result of obstruction
in the arteries or other damage. Such patients live permanently on intravenous
nutrition, as we investigate ways to transplant intestines. This operation is
still very complicated, the results are not yet satisfactory. Consequently,
there are only a small number of centers which perform the procedure. This
procedure could be said to be still in its experimental stages.

Life Expectancy and Future Aspirations

With regard to the subject of life expectancy,
at the end of the first year and after five years following the transplant we
see the best results from kidney transplants from live relative donors. Even
after five years the results in these patients are excellent. Results of kidney
transplants from dead donors are also excellent after a year, and after five
years the figure still remains higher than 75%. Liver transplants also yield
excellent results today: five years following the operation the recipient's
life-expectancy is the same as that of the transplanted organ. Except for rare
cases where repeat transplants are required, the success rate stands above 50%.

The figures for heart transplants are even better. In recent years we
have also seen a considerable improvement in transplants of heart and lungs,
although the five-year prognosis is not as good as that of the first year. Here
the results refer not to the patients but rather to the transplanted organs.
In other words, the number of transplanted organs which continue to function
after one year and after five years. All in all the results are excellent,
signaling a positive forecast for future transplants.

One of the factors that will help to
advance the success of transplants is an intensified fight against rejection
using immunosuppressives. New substances are continuously being sought, and a
long list of substances are being studied. 506FK, 61443RS, Refermicin and
Cytocasein are among those being investigated today for their possible toxic
effects, in order to ascertain whether they may be used in transplants for
improved results.

Another important area, of course, is that of encouraging organ
donation after death. The approach to this subject remains very cautious and
slow, especially here in Israel. But even elsewhere, many countries face severe
problems in this regard.

A further possibility for advancing transplants is
gathering organs from animals, xenografting. Experiments have been carried out
by Prof. Sterszal, including some involving hearts. Such experiments have yet
to show signs of success, but there are those who attach considerable hope to
such a solution, at least for some cases.

Today attempts are being made to increase the use of
organs from live donors. Kidneys, liver, pancreas and large intestine are taken
from live donors, relatives who are prepared to donate part of their organs to
a loved one, most often parents to children, or between siblings.

I have attempted to summarize the current situation
of organ transplants. We hope that in the future, with the further development
of immunosuppressive substances, and with increased awareness in the area of
organ donation, we shall continue to progress.